Terminally differentiating muscle fibers provide an especially useful developmental system with which to examine genetic control of morphogenesis. This utility can be amplified by analysis of muscle differentiation in a eucaryote amenable to genetic and cytogenetic experimentation. In this proposal we will systematically examine the structure and expression of the contractile protein genes which are activated during the differentiation of the indirect flight muscle fibers of Drosophila melanogaster. Using recombinant DNA methodology we will complete the isolation of the contractile protein genes expressed within this tissue. The major structural features of each gene will be determined, and their genomic locations mapped by in situ hybridization to polytene chromosomes. Unique portions of each gene will be used both to monitor contractile protein gene expression during IFM differentiation, and to establish whether these genes are active within any other muscle tissues during Drosophila development. As soon as the genomic location of each gene is known we will begin genetic studies. Gene dosage effects will be investigated in order to establish whether alterations in the relative rates of contractile protein synthesis will disrupt the normal program of myofibril assembly. Lastly we will begin screening for mutant alleles of specific contractile protein genes. The effects of any such mutations on the normal assembly and function of the contractile apparatus will be documented. The long term goals of this project are to enhance our understanding of the mechanisms which coordinate the activities of eucaryotic genes, to help establish the hierarchy of molecular interactions which mediates the assembly of myofibrils, and to further knowledge of molecular aspects of muscle contraction. Such work will likely lead to a better understanding of congenital muscular disorders, particularly the muscular dystrophies.